tbuckley/cabot-search huggingface dataset:
Abstract 10895: Actigraphy-Derived Rest-Activity Rhythms Are Associated With Metabolic Markers and Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Nour Makarem, Marie-Pierre St-Onge, Yifei Sun, Dorothy D Sears, Brooke A Aggarwal, Andrea Baccarelli, Steven Shea, Catherine Marinac, Phyllis Zee, Pamela Ouyang, Susan Redline
Journal: Circulation (2022)

Introduction: Individual behaviors in the 24h rest-activity cycle have been linked to cardiometabolic health (CMH). Studies that integrate the overall multidimensional pattern of 24-h rest-activity rhythms (RAR) and evaluate its unique relation with CMH and type 2 diabetes (T2D) are limited. Hypothesis: Disrupted RAR are associated with poorer glycemic control and T2D. Methods: Participants were n=2127 adults (mean age: 69 ± 9 y, 54% women, 62% non-White) in the MESA Sleep Study (2010-13). Interdaily stability (IS), intradaily variability (IV), most active 10 h period (M10) and least active 5 h period (L5) timing and counts, and relative amplitude (RA) (defined in Table) were derived from 7-d actigraphy data using nonparametric rhythm analysis. Multivariable linear and logistic regression was used to examine cross-sectional and prospective associations with glycemic markers and T2D at baseline and after 6 y of follow-up (2016-18). Results: Higher IS (more stable sleep-wake and rest-activity patterns across days), M10 counts (more active wake period), and RA (greater overall RAR robustness) were related to lower fasting glucose, insulin, and HOMA-IR, while higher IV (more fragmented RAR, less efficient sleep) and L5 counts (less restful sleep) were related to higher levels of these metabolic markers (Table). In cross-sectional and prospective analyses, those in the highest vs. lowest quintile of IS, M10 counts, and RA had up to 75% lower odds of T2D, while being in the highest vs. lowest quintile of IV, L5 counts, and L5 midpoint (later sleep period) was associated with up to 79% higher T2D odds with evidence of a dose-response relationship (p-trend &lt;0.05 for all outcomes). Conclusions: A less robust and stable RAR, lower wake time activity, and a less restful and later sleep period are associated with T2D. Targeting the strength, timing, and regularity of rest-activity and sleep-wake patterns to enhance the rhythmicity of diurnal behaviors may enhance CMH and prevent T2D.
Abstract 10926: Warfarin Dosing Algorithms With the Information on Genotype and Amiodarone for Patients Without Extracorporeal Circulation Devices Could Be Beneficial for Those With Left Ventricular Assist Devices
Authors: Misaki Makiguchi, Makiko Maeda, Marika Saito, Yoshito Ito, Fusako Sera, Takaaki Samura, Takuji Kawamura, Ai Kawamura, Kaoru Kubota, Shinichiro Maeda, Noriyuki Kashiyama, Satoshi Kainuma, Tomohito Ohtani, Daisuke Yoshioka, Toshihiro Takeda, Yoshiki Sawa, Shigeru Miyagawa, Yasushi Sakata, Yasushi Fujio
Journal: Circulation (2022)

Introduction: Many prediction algorithms for warfarin maintenance dose (WD) were constructed based on the clinical and genetic information of the patients without extracorporeal circulation devices (ECDs). However, it is unclear whether might be useful for the patients with ECD, such as left ventricular assist devices (LVAD), who still require warfarin. Hypothesis: The WD algorithms constructed using non-ECD patients could be useful for LVAD patients. Methods: An observational study, the Human Genome Research Ethics Committee of OU approved (#756), was conducted at the Osaka University (OU) Hospital on 108 LVAD patients receiving warfarin therapy. Genetic polymorphisms of CYP2C9*1, *3, and VKORC1-1639G&gt;A were tested using TaqMan genotyping assay kits. WD was defined as the administered dose during the periods when the PT-INR value was within its target range. We investigated the difference between the actual warfarin dose (AWD) and the calculated warfarin dose (CWD) using an algorithm proposed by the International Warfarin Pharmacogenetics Consortium (IWPC), which we verified with 125 Japanese non-ECD patients previously (Eur J Clin Pharmacol, 75:901). Results: The percentage of patients whose difference between CWD and AWD was within 20% of AWD showed no significant difference between the LVAD and the non-ECD (%; I, LVAD, 41.7, non-ECD, 49.6, p=0.23). The root mean squared percentage error (RMSPE) to the AWD was similar between the groups (%; LVAD, 42, non-ECD, 37). As the algorithm requires if amiodarone is concomitant with warfarin, we probed the effect of the amiodarone dose on the CWD. Interestingly, RMSPE of the LVAD with ≥ 200 mg/day of amiodarone (≥ 200A) was higher compared to those with &lt; 200 mg/day (&lt;200A) and without amiodarone (%; 85.5, 25.9, 36.8). The difference between AWD and CWD of ≥ 200A was significantly higher than &lt;200A (mg/day; 0.87, -0.07; p=0.012). We verified similar tendencies using other algorithms published before. Conclusions: The WD algorithm with the information on genotype and concomitant use of amiodarone for the non-ECD could be beneficial for the LVAD. Besides them, extra careful attention should be required for patients with ≥ 200 mg/day of amiodarone not to have warfarin overdosed.
Abstract 10250: Association of Nutritional Status With Symptoms and Quality of Life After Aortic Valve Replacement
Authors: Heikki J Niemi, Minna Kylmälä, helena rajala, Jyri Lommi, Satu Suihko
Journal: Circulation (2022)

Introduction: Most patients with aortic stenosis (AS) are elderly and have multiple comorbidities. These conditions are often associated with poor nutrition and frailty. The purpose of this study was to assess the impact of preoperative nutritional status on symptoms and quality of life (QOL) after aortic valve replacement. Methods: We prospectively studied 220 patients with severe AS. Nutritional status was assessed using the Mini Nutritional Assessment (MNA) questionnaire. A score below 24 out of 30 indicates risk of malnutrition. Patients were evaluated preoperatively and three months after intervention. QOL was assessed using the RAND 36-item health survey. The six-minute walking test (6MWT) and the five times sit to stand test (5TSTS) were performed in 92 and 87 patients, respectively. Results: MNA score was below 24 in 28 % of the patients. Age, BMI, sex, and the proportion of patients undergoing surgery or TAVI were similar between MNA &lt; 24 and MNA &gt; 24 groups. There were no differences in NYHA class preoperatively, however a larger proportion of patients with MNA &lt; 24 remained in NYHA 2 or higher after intervention (42 % vs 25 %, p = 0.03). They also remained more symptomatic, with dyspnea in 28 % vs 12 % (p = 0.01) and decreased exercise capacity in 44 % vs 16 % (p &lt; 0.001) of the patients. Postoperative QOL was worse in patients with MNA &lt; 24, with significant differences in seven categories (Figure). They performed worse in 6MWT at baseline (median 380 m vs 480 m, p = 0.02), but the difference was not significant after intervention (480 m vs 499 m, p = 0.4). Difference in 5TSTS was not significant at baseline (13.45 s vs 11 s, p = 0.1), but they performed worse after intervention (14.95 s vs 10.8 s, p = 0.02). Conclusions: Malnutrition is common among AS patients and is associated with worse QOL and more symptoms after intervention. Nutritional status should be assessed in AS patients before intervention for risk stratification and to find patients who might benefit from nutritional intervention.
Abstract 10434: Very Late Stent Thrombosis Caused by Rupture of In-Stent Neoatherosclerosis 15-Years After Bare Nitinol Stent Implantation in Superficial Femoral Artery Visualized With Multimodality Imaging
Authors: Taku Toyoshima, Osamu Iida, Mitsutoshi Asai, masaharu masuda, Shin Okamoto, Takayuki Ishihara, Kiyonori Nanto, Takuya Tsujimura, Yasuhiro Matsuda, Yosuke Hata, Hiroyuki Uematsu, Naoko Higashino, Sho Nakao, Toshiaki Mano
Journal: Circulation (2022)

A 77-year-old man complained of intractable rest pain in his left leg, which occurred one week before hospital admission. His past medical history included diabetes mellitus and history of smoking. He was prescribed cilostazol for treatment of peripheral vascular disease. He underwent endovascular therapy (EVT) 15-years earlier with a bare nitinol stent (BNS) implantation in his left superficial femoral artery (SFA), and no restenosis was detected by annual duplex ultrasound (DUS) follow-up until this session. DUS observed restenosis with 14.8 peak systolic velocity ratio, and initial angiography ( Panel A , white arrow) revealed subtotal occlusion at the stented lesion. Intravascular angioscopy ( Panel C ) demonstrated disrupted cavity with red thrombus attached. Optical frequency domain imaging (OFDI) ( Panel D ) and intravascular ultrasound (IVUS) ( Panel E ) demonstrated fibrous cap disruption with a clear cavity formed inside the plaque (6 to 11 o’clock in Panel D and E), as well as thin sheet calcification. The other side (11 to 6 o’clock) shows a signal rich region with high attenuation that indicates fibroatheroma. The lesion was diagnosed as very late stent thrombosis (VLST) because multimodality images revealed rupture of in-stent neoatherosclerosis with red thrombus attached. After successful vessel preparation with a high-pressure 6mm balloon, 6 mm drug-coated balloons were used. The completion angiogram revealed an acceptable result with neither residual stenosis nor flow-limiting dissection ( Panel B ). Neoatherosclerosis has been reported as one of the major causes of VLST in the coronary arteries; however, it has rarely been reported in the peripheral arteries. This case illustrates valuable direct visualization with multimodality imaging of a case with VLST caused by rupture of in-stent neoatherosclerosis 15-years after BNS implantation, and the value of multimodality imaging for comprehensive evaluation to diagnose the mechanism of VLST in SFA.
Abstract 10267: Decreasing Hospitalization Rate and Improvement in Mortality Following Acute Haemorrhagic Stroke From 2002-2017: An Australian Statewide Cohort Study of 35433 Patients
Authors: Arielle C Hsu, Vijayatubini Vijayarajan, Yeu-Yao Cheng, Matthew Wei Shun Shun, Karice HYUN, Vincent Chow, David Brieger, Leonard Kritharides, Chin Chwan NG
Journal: Circulation (2022)

INTRODUCTION: Haemorrhagic stroke (HS) is an important cardiovascular cause of mortality worldwide. In Australia, long term temporal trends in HS hospitalisation rates and predictors of mortality are unknown. Methods: All New South Wales residents with first-ever HS from 2002-2017 were identified from the Centre-for-Health-Record-Linkage statewide databases. Mortality tracked to 31 Dec 2018 via the death registry were adjusted for age, sex, admission year, referral source, surgical evacuation of HS status, and comorbidities in multivariable regression analyses. Results: There were 35433 patients (51% male) admitted for HS. Age-adjusted mean (±SD) admission rates were higher for males than females (63.6±6.2 vs 49.9±4.4 admissions-per-100,000-persons-per-annum respectively, p&lt;0.001). Annual admission rates declined for both sexes from 2002-2017 (male: 74.4 to 52.5 vs female: 55.2 to 43.6 admissions-per-100,000-persons, both p&lt;0.001 for linear trend). Admission rates were highest in patients ≥60yo but significantly declined from 2002-2017 in both sexes, while admission rates for &lt;60yo patients remained static. Crude in-hospital and 1-year mortality post-HS were 22.5% and 38.2% respectively. Adjusted in-hospital and 1-year mortality post-HS were lower in 2017 compared to 2002 (adjusted odds ratio [aOR]=0.56, 95% confidence interval [CI]=0.49-0.65; adjusted hazard ratio [aHR]=0.73, 95%CI=0.66-0.80, respectively) (all p&lt;0.001). Annual rates of surgical evacuation were static during study period (10.4% per year). Surgical evacuation was associated with better in-hospital and 1-year mortality (aOR=0.47, 95%CI=0.42-0.53; aHR=0.49, 95%CI=0.45-0.53, both p&lt;0.001 respectively). Increasing age and higher Charlson comorbidity index independently predicted greater in-hospital and 1-year mortality. Male sex was associated with lower in-hospital mortality (aOR=0.88, 95%CI=0.83-0.93, p&lt;0.001) but not at 1-year. Conclusion: Age-adjusted admission rates for HS fell between 2002-2017 for both sexes, driven mostly by ≥60 age groups, with adjusted in-hospital and 1-year mortality improving by 43% and 27% respectively. Strategies to improve survival including greater access to surgical evacuation should be further explored.
Abstract 10942: The A Body Shape Index and Type 2 Diabetes Are Mutually Independent Predictors of Major Cardiovascular Events in Patients With Established Cardiovascular Disease
Authors: Lukas Sprenger, Maximilian Maechler, Alexander Vonbank, Barbara Larcher, Arthur Mader, Andreas Leiherer, Axel Muendlein, Heinz Drexel, Christoph H Saely
Journal: Circulation (2022)

Introduction: The A Body Shape index (ABSI) is a validated measure of visceral adiposity that is calculated based on waist circumference, height and BMI. Hypothesis: We hypothesize that ABSI is a predictor of major cardiovascular events in patients with established cardiovascular disease (CVD). Methods: We prospectively recorded cardiovascular events in a large cohort of 1544 patients with established CVD (1297 patients with angiographically proven stable coronary artery disease and 247 patients with sonographically verified PAD) over a mean follow-up time of 10.0±4.6 years. Results: At baseline, the ABSI was higher in patients with type 2 diabetes (T2DM; n=502) than in those who did not have diabetes (8.4±0.6 vs. 8.3±0.6; p&lt;0.001). Prospectively, the ABSI significantly predicted the incidence of MACE (n=507) after adjustment for age, gender, smoking, hypertension, LDL cholesterol, HDL cholesterol, and T2DM (standardized adjusted HRs 1.14 [1.04-1.24]; p=0.004, respectively). T2DM in turn in this model also significantly predicted MACE with a HR of 1.61 [1.33-1.94]; p&lt;0.001 after adjustment for ABSI. Conclusions: We conclude that ABSI and T2DM are mutually independent risk factors for MACE in patients with established cardiovascular disease.
Abstract 10265: Association of Myocardial Mechanical Markers of Extracellular Volume Expansion With Heart Failure and All-Cause Mortality: The Multi-Ethnic Study of Atherosclerosis
Authors: Vinithra Varadarajan, Sharmila Dorbala, Karol E Watson, Hieu Nguyen, Bharath Ambale Venkatesh, Joao A Ac Lima, Steven Shea, Wendy S Post, Robyn McClelland, Collin Wu
Journal: Circulation (2022)

Introduction: Characteristic myocardial deformation indices have been proposed to be associated with extracellular volume (ECV) expansion and differentiate cardiac pathologies that induce cardiac remodeling. Hypothesis: Our hypothesis was that such mechanical markers are associated with (1) pathologic ECV expansion and cardiac remodeling and (2) clinical outcomes of heart failure and mortality. Methods: Our analysis included 2778 participants who underwent cardiac MRI at the Multi-Ethnic Study of Atherosclerosis Exam 5 (2010-2012). The following deformation indices were calculated: relative apical strain ratio (RAS), septal apical basal ratio (SAB) and ejection fraction circumferential strain ratios (EFSR). We used linear regression to analyze the associations of these deformation indices with cardiac remodeling and ECV expansion. We used Cox proportional models to investigate the associations of mechanical deformation indices with incident HF and all-cause mortality. Results: The mean (SD) age of the cohort at Exam 5 was 69.1 (9.3) years; 53% were female. MRI tagging and T1 mapping analyses showed that higher levels of EFSR were associated with 0.2% greater ECV and 4.4ms higher native T1. In addition, EFSR was associated with 3.59ml lower LV end-diastolic volume, 1.98g higher LV mass and 0.13 ⃘ higher torsion. EFSR was associated with greater LA volume, decreased total emptying fraction and reduced maximal strain (Table 1). During a follow-up period of 7.5 years (Figure 1), there were 101 incident heart failure events, and 228 all-cause deaths. In the multivariable cox regression analysis, hazard ratios (95% CI) of incident HF and all-cause mortality for each unit increase of EFSR were 1.36 (1.04,1.78) and 1.31 (1.05,1.64) (Table 2), respectively. Conclusion: Mechanical markers of extracellular expansion are associated with adverse cardiac remodeling, incident HF and all-cause mortality.
Abstract 10914: Acute Heart Failure Due to Rupture of an Aortic Pseudoaneurysm Into the Right Atrium
Authors: Nobunari Tomura, Takuo Nakagami, Masakazu Kikai, Tetsuro Hamaoka, Kuniyoshi Fukai, Shinichiro YAMAGUCHI, Keiji Matsubayashi, Satoaki Matoba
Journal: Circulation (2022)

Introduction: Rupture of an aortic aneurysm into the right atrium (RA) is extremely rare, while rupture into the thoracic cavity or pericardial sac is a common fatal complication. We describe a case of acute heart failure due to rupture of an aortic pseudoaneurysm with aorta-right atrial fistula. Case Summary: A 73-year-old man presented to the emergency department with dyspnea and abdominal distention. He had a history of ascending aortic replacement for type A aortic dissection 18 years ago. On arrival, physical examination revealed diminished breath sounds, leg edema but no cardiac murmurs. Investigations demonstrated abnormality of hepatic and kidney function, elevated BNP (490.9 pg/ml) in blood exam, and enlargement of ascending aortic aneurysm at the proximal anastomotic site with ascites/pleural effusion on computed tomography (CT), while left ventricular function was normal on transthoracic echocardiogram. We diagnosed acute heart failure with preserved ejection fraction and started to reduce fluid using diuretics. However, the response to diuretics was not good and the progression of lactic acidosis was observed regardless of using cardiotonic agent. Since it was becoming difficult to maintain systemic circulation, we performed further investigations before introducing mechanical support. The pulmonary artery catheterization revealed elevated RA pressure with wide pulse pressure (38/12 mmHg) and Oxygen step up in RA. An aortic root angiogram, contrast-enhanced CT and transesophageal echocardiogram showed a rupture of aortic pseudoaneurysm complicated with aorta-right atrial fistula (Figure). Although emergent surgery was performed, he unfortunately died the following day. Conclusions: This is a rare case of intracardiac perforation of aortic aneurysm diagnosed by various modalities. We should consider the possibility of developing shunt disease when we meet patients with rapidly progressive circulatory failure unresponsive to drugs.
Abstract 10353: Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3 Year Results of the SUCCOUR Trial
Authors: Tomoko Negishi, Paaladinesh Thavendiranathan, Kazuaki Negishi, Martin Penicka, Julie Lemieux, Klaus Murbraech, Sakiko Miyazaki, Mitra Shirazi, Ciro Santoro, Goo-Yeong Cho, Bogdan A Popescu, Wojciech Kosmala, Ben Costello, Andre La Gerche, Philip Mottram, Liza Thomas, Stephanie Seldrum, Krasimira Hristova, Manish Bansal, Koji Kurosawa, Nobuaki Fukuda, Hirotsugu Yamada, Masaki Izumo, Kazuko Tajiri, Maciej Sinski, Dragos Vinereanu, Evgeny Shkolnik, Jose Banchs, Shelby Kutty, Thomas Marwick
Journal: Circulation (2022)

Introduction: Global longitudinal strain (GLS) can predict cancer therapeutics-related cardiac dysfunction (CTRCD) and guide initiation of cardioprotection (CPT) at the time of chemotherapy. No prospective randomized controlled trial (RCT) has identified the impact on LV function in survivors. Hypothesis: GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care. Methods: In this international (28 sites) multicenter prospective RCT, patients (pts) were included if they were administrated anthracyclines and had another risk factor for HF. They were randomly allocated into undergoing GLS-guided CPT for &gt;12% relative reduction in GLS or EF-guided CPT for &gt;10% absolute reduction of EF. Primary endpoint was the change in EF (ΔEF) from baseline to 3 years by 3D echocardiography. Results: Among 331 pts enrolled, 255 (77%, 60±16 years, 95% women) completed 3-year follow-up (123 in EF-guided group and 132 in GLS-guided). Most had breast cancer (236, 93%), 67 (26%) with hypertension and 32 (13%) with diabetes mellitus. A regimen of anthracycline and trastuzumab was the most common chemotherapy regimen (84%). The baseline LVEF was 61±4% with GLS of 20.7±2.3% in the entire population. CPT was administrated in 18 pts (15%) in EF-guided and 41 (31%) in GLS-guided (p=0.02). Most patients showed recovery in EF and GLS after chemotherapy (Figure). ΔEF was -2.0±4.8 in EF-guided and -1.4±5.4 in GLS-guided (p=0.25), but LVEF at 3 years in EF-guided was lower than that of GLS-guided (58.0±5.6% vs 59±4.9%, p=0.043). Ten pts in EF-guided developed CTRCD, and 6 in GLS-guided (p=0.24). Conclusions: Most of the enrolled pts were taking potentially cardiotoxic chemotherapy for breast cancer. Almost all improved LV function over 3 years, and although GLS-guided CPT was associated with higher EF at 3 years, there was no difference in ΔEF compared with EF-guided surveillance.
Abstract 10461: Single-Cell Transcriptional Analysis of Altered Cardiomyocyte Pdk4 as Indicator of Ischemic Stress Vulnerability in Aging
Authors: Mohammad Fatmi, Di Ren, Hao Wang, Linda Ines Zoungrana, Meredith Krause-Hauch, Ji Li
Journal: Circulation (2022)

Introduction: The mechanisms by which aging increases vulnerability to ischemic insult are not well understood. Single-Cell RNA sequencing (scRNA seq) was employed to characterize transcriptional differences in various cell types between aged and young mice which may contribute to aged-related vulnerability to ischemic insult. Pyruvate Dehydrogenase Kinase 4 (Pdk4) has been shown to impact capacity for fatty-acid oxidation (FAO) and consequently adaption to metabolic alterations of ischemic insult. Hypothesis: Alteration of Pdk4 expression levels is an adaptive response transcriptionally under pathological stress to maintain metabolic homeostasis during ischemia and reperfusion (I/R). Methods: Young (3-5 months) and aged (24-26 months) C57BL/6J mice were subjected to in vivo regional 45 min of ischemia and 24 hr of reperfusion (I/R) or sham operations. Bioinformatic analysis was done using Seurat integration vignettes allowing for cell type identification and differential expression testing. Observing genetic expression profiles by cell types. Substrate metabolism was determined with working heart system and Seahorse XF Analyzer. Results: Pdk4 was profoundly found in cardiomyocytes versus fibroblasts, endothelial cells and macrophages of both young and aged hearts. Interestingly, I/R stress triggered Pdk4 mRNA expression of young but not aged cardiomyocytes. Moreover, there is a relative higher Pdk4 level in aged versus young cardiomyocytes under sham operations, indicating Pdk4 mRNA respond to pathological stress. The ex vivo working heart perfusion data showed that young versus aged hearts exhibited higher FAO in response to I/R. Moreover, Seahorse XF Analyzer showed a higher glycolysis rate in young versus aged cardiomyocytes during I/R. It suggests that an impaired cardiomyocyte Pdk4 mRNA response occurred in aging under I/R stress conditions, this could result in cardiac maladaptive metabolic alterations in aging during pathological stress. Conclusions: Alterations in Pdk4 levels of cardiomyocytes regulates cardiac adaptive metabolism in response to pathological stress. This adaptive regulation of cardiomyocyte Pdk4 is impaired in aging that leads to more vulnerability of aged versus young hearts to ischemic insult.